Small Intraductal Papillary Mucinous Neoplasm Research Articles

Multifocal lesions in intraductal papillary mucinous neoplasms: Intraoperative pancreatic juice cytology

On radiological study, 25% to 41% of the patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have multifocal lesions. On the other hand, in pathological assessment, most of these patients had lots of micro premalignant lesions such as small IPMNs and pancreatic intraepitehrial neoplasms (PanINs) in the background pancreas, indicating that all the pancreas having IPMNs have a potential to develop multifocal lesions. There are 3 possible types of multifocal lesions in patients with IPMNs, namely multiple branch duct IPMNs (BD-IPMNs) by multicentric development, multiple main duct or mixed type IPMNs (MD- or Mix-IPMNs) by the mechanism of intraductal dissemination of the neoplastic cells [1,2], and the development of pancreatic ductal adenocarcinoma (PDAC) concomitant with IPMNs [3,4]. Pancreatic juice cytology under endoscopic retrograde pancreatography is reported to leads early detection of concomitant PDAC during assessment of IPMNs [5], while it is often difficult to determine the location of malignant lesions when pancreatography and other imaging modalities cannot provide any significant abnormalities. Therefore, the role of intraoperative pancreatic juice cytology is to determine whether such lesions which are not detected by preoperative assessment might left in the remnant pancreas during partial pancreatectomy for IPMN. Previous report [6] demonstrated that in consecutive 48 patients who underwent intraoperative irrigation cytology in the remnant pancreas during partial pancreatectomy for IPMN, 5 patients had positive results and subsequently underwent additional resection of the pancreas. High-risk lesions including 4 PanIN-3 lesions and one invasive carcinoma were detected in all 5 additionally resected specimens. On the other hand, there might be possible patients who might have false negative result of intraoperative irrigation cytology [7] or peritoneal dissemination because of leakage of irrigation solution containing cells from high-risk lesions. In this presentation, roles and limitations of intraoperative pancreatic juice cytology will be discussed.

Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a noninvasive epithelial neoplasm of mucin-producing cells arising in the main duct (MD) and/or branch ducts (BD) of the pancreas. Involved ducts are dilated and filled with neoplastic papillae and mucus in variable intensity. IPMN lacks ovarian-type stroma, unlike mucinous cystic neoplasm, and is defined as a grossly visible entity (≥ 5 mm), unlike pancreatic intraepithelial neoplasm. With the use of high-resolution imaging techniques, very small IPMNs are increasingly being identified. Most IPMNs are solitary and located in the pancreatic head, although 20%-40% are multifocal. Macroscopic classification in MD type, BD type and mixed or combined type reflects biological differences with important prognostic and preoperative clinical management implications. Based on cytoarchitectural atypia, IPMN is classified into low-grade, intermediate-grade and high-grade dysplasia. Based on histological features and mucin (MUC) immunophenotype, IPMNs are classified into gastric, intestinal, pancreatobiliary and oncocytic types. These different phenotypes can be observed together, with the IPMN classified according to the predominant type. Two pathways have been suggested: gastric phenotype corresponds to less aggressive uncommitted cells (MUC1 -, MUC2 -, MUC5AC +, MUC6 +) with the capacity to evolve to intestinal phenotype (intestinal pathway) (MUC1 -, MUC2 +, MUC5AC +, MUC6 - or weak +) or pancreatobiliary /oncocytic phenotypes (pyloropancreatic pathway) (MUC1 +, MUC 2-, MUC5AC +, MUC 6 +) becoming more aggressive. Prognosis of IPMN is excellent but critically worsens when invasive carcinoma arises (about 40% of IPMNs), except in some cases of minimal invasion. The clinical challenge is to establish which IPMNs should be removed because of their higher risk of developing invasive cancer. Once resected, they must be extensively sampled or, much better, submitted in its entirety for microscopic study to completely rule out associated invasive carcinoma.

小型膵管内乳頭粘液性腫瘍からの発生が示唆された浸潤型膵癌の2例

小型膵管内乳頭粘液性腫瘍からの発生が示唆された浸潤型膵癌の2例

Cytological analysis of small branch-duct intraductal papillary mucinous neoplasms provides a more accurate risk assessment of malignancy than symptoms

Objectives:The Sendai guidelines for management of patients with clinically suspected intraductal papillary mucinous neoplasms (IPMN) recommend resection of cysts > 30 mm, a dilated main pancreatic duct (MPD) > 6 mm, a mural nodule (MN), symptoms or positive cytology. Although sensitive, asymptomatic cysts, nonspecific symptoms, and a high threshold for positive cytology limit the specificity of the guidelines. We have assessed the value of cytology relative to symptom for predicting malignancy in IPMNs without high-risk imaging features.Materials and Methods:We retrospectively reviewed the clinical, radiological, and cytological data of 31 small branch-duct IPMNs without a MN. The cytological presence of high-grade atypical epithelial cells (HGA) was considered true positive, with a corresponding histology of high-grade dysplasia or invasive carcinoma. The performance of cytology versus symptoms was evaluated by calculating the sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy.Results:The sensitivity (0.80), specificity (0.85), and accuracy (0.84) of HGA were higher than the corresponding performance characteristics of symptoms (0.60, 0.45, and 0.48, respectively). The NPV of no HGA on cytology was > 95%.Conclusions:Cytology is a better predictor of malignancy than symptoms, for the conservative management of small branch-duct IPMNs. Cytology contributes to a highly accurate triple negative test for malignancy in small IPMN: No dilated MPD, MN or HGA.

Intraductal papillary mucinous neoplasm

Intraductal papillary mucinous neoplasm (IPMN) is a grossly visible (≥1 cm), mucin-producing neoplasm that arises in the main pancreatic duct and/or its branches. Patients with intraductal papillary mucinous neoplasm can present with symptoms caused by obstruction of the pancreatic duct system, or they can be asymptomatic. There are 3 clinical subtypes of intraductal papillary mucinous neoplasm: main duct, branch duct, and mixed. Five histologic types of intraductal papillary mucinous neoplasm are recognized: gastric foveolar type, intestinal type, pancreatobiliary type, intraductal oncocytic papillary neoplasm, and intraductal tubulopapillary neoplasm. Noninvasive intraductal papillary mucinous neoplasms are classified into 3 grades based on the degree of cytoarchitectural atypia: low-, intermediate-, and high-grade dysplasia. The most important prognosticator, however, is the presence or absence of an associated invasive carcinoma. Some main duct-intraductal papillary mucinous neoplasms progress into invasive carcinoma, mainly tubular adenocarcinoma (conventional pancreatic ductal adenocarcinoma) and colloid carcinoma. Branch duct-intraductal papillary mucinous neoplasms have a low risk for malignant transformation. Preoperative prediction of the malignant potential of an intraductal papillary mucinous neoplasm is of growing importance because pancreatic surgery has its complications, and many small intraductal papillary mucinous neoplasms, especially branch duct-intraductal papillary mucinous neoplasms, have an extremely low risk of progressing to an invasive cancer. Although most clinical decision making relies on imaging, a better understanding of the molecular genetics of intraductal papillary mucinous neoplasm could help identify molecular markers of high-risk lesions. When surgery is performed, intraoperative frozen section assessment of the pancreatic resection margin can guide the extent of resection. Intraductal papillary mucinous neoplasms are often multifocal, and surgically resected patients should be followed for metachronous disease.

Optimal management of the branch duct type intraductal papillary mucinous neoplasms of the pancreas.

To determine the optimal management of the intraductal papillary mucinous neoplasms (IPMNs) according to the morphologic type based on distinguishing between benign and malignant diseases. IPMNs are increasingly recognized clinicopathologic entity. Extended pancreatic resection with radical lymph node dissection has been recommended for treatment. A retrospective clinicopathologic study was carried out of the 57 cases with IPMNs who were treated between 1985 and 2001. Forty-three patients with IPMNs underwent resection, and 14 patients with small IPMNs were observed without resection. Among the 43 resected IPMNs, 25 were benign and 18 were malignant. Malignant tumors were significantly greater in diameter than benign tumors (52.9 vs. 30.2 mm, P< 0.05). All main duct type tumors with mural nodules were malignant. All branch duct type tumors less than 30 mm in diameter and without mural nodules were benign. Twelve branch duct type IPMNs size less than 30 mm were not resected and have not progressed. These results suggest that the branch duct type IPMNs less than 30 mm and without mural nodules is benign and might be treatable with limited resection or careful observation.